18 January 2011 EMA/COMP/642562/2010 Committee for Orphan Medicinal Products

Public summary of opinion on orphan designation Silibinin-C-2',3-dihydrogensuccinate, disodium salt for the prevention of recurrent hepatitis C in liver transplant recipients

On 17 December 2010, orphan designation (EU/3/10/828) was granted by the European Commission to Rottapharm S.p.A., Italy, for silibinin-C-2',3-dihydrogensuccinate, disodium salt for the prevention of recurrent hepatitis C in liver transplant recipients.

What is recurrent hepatitis C in liver transplant recipients? Hepatitis C is an infection of the liver due to the hepatitis C virus. Patients with chronic (long-term) infection are at risk of liver damage and may develop serious liver diseases such as cirrhosis (liver scarring) and liver cancer, which require liver transplantation. However, because the hepatitis C virus remains in the body, the transplanted liver is also at risk of becoming infected, and therefore of developing cirrhosis and cancer. Recurrent (repeated) hepatitis C in liver transplant recipients is a debilitating and life-threatening condition because of the serious complications that can develop in the transplanted liver.

What is the estimated number of patients at risk of developing the condition? At the time of designation, the number of liver transplant recipients at risk of developing recurrent hepatitis C was estimated to be less than 1 people in 10,000 in the European Union (EU)* . This is equivalent to a total of fewer than 51,000 people, which is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*

Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 27), Norway, Iceland and Liechtenstein. This represents a population of 506,500,000 (Eurostat 2010).

7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7523 7040 E-mail [email protected] Website www.ema.europa.eu

An agency of the European Union

© European Medicines Agency, 2011. Reproduction is authorised provided the source is acknowledged.

What methods of prevention are available? At the time of designation, there were no satisfactory treatments authorised for the prevention of recurrent hepatitis C in liver transplant recipients. Patients at risk were treated using the ‘standard of care’ for hepatitis C (pegylated interferon and ribavirin).

How is this medicine expected to work? Silibinin-C-2',3-dihydrogensuccinate, disodium salt is made from a substance extracted from milk thistle fruits. It has been used since the mid-1980s as an antidote to poisoning with the fungus Amanita phalloides. In the prevention of hepatitis C recurrence in liver transplant recipients, it is expected to work as an antiviral medicine by stopping the hepatitis C virus from multiplying. When given at the time of liver transplantation, this is expected to rid the body of the virus, therefore preventing the transplanted liver from becoming infected at a later date.

What is the stage of development of this medicine? The effects of silibinin-C-2',3-dihydrogensuccinate, disodium salt have been evaluated in experimental models. At the time of submission of the application for orphan designation, clinical trials with the medicine in liver transplant recipients at risk of developing recurrent hepatitis C were ongoing. At the time of submission, the medicine was authorised in 15 countries in the EU for the treatment of liver intoxication due to Amanita phalloides under the trade name Legalon SIL. The medicine was not authorised anywhere in the EU for the prevention of recurrent hepatitis C in liver transplant recipients nor designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 October 2010 recommending the granting of this designation.

__________________________

Opinions on orphan medicinal product designations are based on the following three criteria: 

the seriousness of the condition;



the existence of alternative methods of diagnosis, prevention or treatment;



either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.

Public summary of opinion on orphan designation EMA/642562/2010

Page 2/5

For more information Sponsor’s contact details: Rottapharm S.p.A Galleria Unione, 5 20122 Milan Italy Postal Address: Rottapharm S.p.A. Via Valosa di Sopra, 9 20900 Monza (MB) Italy Telephone: +39 039 73 90 256 Telefax: +39 039 73 90 269 E-mail: [email protected]

For contact details of patients’ organisations whose activities are targeted at rare diseases see: 

Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe.



European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.

Public summary of opinion on orphan designation EMA/642562/2010

Page 3/5

Translations of the active ingredient and indication in all official EU languages 1 , Norwegian and Icelandic Language

Active ingredient

Indication

English

Silibinin-C-2',3-dihydrogensuccinate,

Prevention of recurrent hepatitis C in liver

disodium salt

transplant recipients

Силибинин-C-2',3-дихидрогенсуксинат,

Превенция на рекурентен Хепатит С при

двунатриева сол

пациенти, получили чернодробни

Bulgarian

транспланти Czech Danish Dutch Estonian Finnish French German

Disodná sůl silibinin-C-2',3-

Léčba pravostranného srdečního selhání

dihydrogensukcinátu

po kardiotomii

Silibinin-C-2',3-dihydrogensuccinat,

Forebyggelse af tilbagevendende hepatitis

dinatriumsalt

C i levertransplantatmodtagere

Silibinine-C-2',3-diwaterstofsuccinaat,

Preventie van recurrente hepatitis C in

dinatriumzout

levertransplantrecipiënten

Silibiniin-C-2',3-divesiniksuktsinaadi

Retsidiivse C-hepatiidi ärahoidmine

dinaatriumsool

maksatransplantaadi retsipientidel.

Silibiniini-C-2',3-divetysukkinaatti,

Toistuvan hepatiitti C:n esto

dinatriumsuola

maksansiirtojen vastaanottajissa

Silibiline-C-2',3-dihydroxysuccinate, sel

Prévention des recurrences de l'hépatite

disodique

virale C chez les transplantés hépatiques

Dinatrium(silibinin-C-2',3-disuccinat)

Prävention rezidivierender Hepatitis CInfektionen bei Lebertransplantatempfängern

Greek Hungarian Italian Latvian Lithuanian

Σιλιβινίνη-C-2',3-δισόξινη ηλεκτρική,

Πρόληψη ηποτροπιάζουσας Ηπατίτιδας C σε

δινάτριο άλας

λήπτες μοσχεύματος ήπατος

Szilibinin-C-2',3-dihidrogén-szukcinát

Májtranszplantációt követő visszatérő

dinátrium sója

Hepatitis –C megelőzése

Silibinina-C-2',3-diidrogenosuccinato, sale

Prevenzione delle recidive dell’epatite C in

disodico

pazienti sottoposti a trapianto di fegato

Silibinīna-C-2',3-dihidrogēnsukcināta

C hepatīta recidīva profilakse aknu

dinātrija sāls

transplantāta recipientiem

Silibinino-C-2',3-dihidrogensukcinatas,

Pakartotinio hepatito C viruso kepenyse

dinatrio druska

prevencija, kepenų transplanto recipientams

Maltese Polish

Silibinin-C-2',3-dihydrogensuccinate,

Prevenzjoni tal-epatite tat-tip Ċ rikorrenti

disodium salt

f’pazjenti li kellhom trapjant tal-fwied

Sylibino-C-2',3-dwuwodorobursztynian, sól

Zapobieganie nawracającemu zapaleniu

dwusodowa

wątroby typu C u biorców przeszczepu wątroby

Portuguese Romanian Slovak

1

Silibinina-C-2',3-di-hidrogenossucinato, sal

Prevenção da hepatite C recorrente em

dissódico

receptores de transplante hepático

Silibină-C-2',3-dihidrogen succinat, sare

Profilaxia hepatitei C recurente la pacienţii

disodică

cu transplant hepatic

Dvojsodná soľ silibinín-C-2',3-

Prevencia rekurentnej hepatitídy C u

dihydrogénsukcinátu

pacientov po transplantácii pečene

At the time of designation

Public summary of opinion on orphan designation EMA/642562/2010

Page 4/5

Slovenian Spanish Swedish Norwegian Icelandic

Silibinin-C-2',3-dihidrogensukcinat,

Preprečevanje rekurentnega hepatitisa C

dinatrijeva sol

pri bolnikih z jetrnim poresadkom

Silibinina-C-2',3-dihidrógeno-succinato, sal

Prevención de la recurrencia de la hepatitis

disódica

C en recipientes de transplante de hígado

Silibinin-C-2',3-divätesuccinat,

Profylax av återkommande hepatit C hos

dinatriumsalt

levertransplantat mottagare

Silibinin-C-2',3-dihydrogensuksinat,

Forebygging av hepatitt C residiv hos

dinatriumsalt

mottagere av levertransplantat

Silibinin-C-2',3-tvíhýdrógen súkkínat,

Fyrirbyggjandi gegn endurvakinni

tvínatríum salt

lifrarbólgu C lifrarsjúkdómi hjá lifrarígræðsluþegum

Public summary of opinion on orphan designation EMA/642562/2010

Page 5/5